The ability to perform molecular analyses of chemical and biological systems has grown tremendously in recent years. For example, crystallographic analysis is now available for a variety of molecules, including complex proteins and nucleic acids that were once thought to be uncrystallizable. High-quality crystals of these molecules can be analyzed by x-ray diffraction techniques to produce accurate three-dimensional molecular structures. This 3-D structure information can then be utilized to predict functionality and behavior of the molecule.
However, even today it is still often very difficult to form a high-quality crystal of a complex molecule, requiring a lot of trial and error-not to mention patience and persistence-on the part of the researcher. The large, complex molecular structures of many biological compounds makes them resistant to forming highly ordered crystal structures. Successful crystallization typically requires methodical experimentation with large numbers of reagents and crystallization parameters such as concentration, temperature, solvent type, countersolvent type, and time, among other parameters.
There have also been a lot of advancements in molecular and cellular analysis techniques such as DNA sequencing, gene cloning, monoclonal antibody production, cell transfection, and amplification techniques (such as PCR), among others. Like crystallization, the success of these techniques depends in large measure on the ability to try many possible combinations of samples and reaction environments in hopes of discovering a combination that will permit the analysis.
These “high-throughput” techniques often use densely packed microtiter plates made up of arrays of small volume wells each having a unique combination of reaction conditions (e.g., reagent types, concentrations, etc.). Because the top of the wells are normally left uncovered, control of the reaction environment is limited, and environmental contaminants and fluid evaporation are often a significant problem.
Micro-fluidic pump and valve systems can address the exposure problems by delivering samples and reagents to sealed reaction chambers that are sealed off from the ambient atmosphere. These systems work well carrying out liquid and solution phase reactions in a highly controlled environment. However, when solid-phase products are formed, such as through precipitation or freezing, the micro-fluidic systems can have a difficult time transporting the solids to a point where additional analysis is performed. Ironically, solid samples formed in uncovered microtiter plate wells are easier to access and transport than the solids formed in the micro-fluidic systems. Thus, there is a need for micro-fluidic systems that make it easier to access and transport products from the reaction chambers. This and other problems are addressed by embodiments of the invention.